Maprotiline Hydrochloride

MOLECULAR FORMULA :

C20-H23-N.Cl-H

MOLECULAR WEIGHT :

313.90

WISWESSER LINE NOTATION :

L6 H666/GP 2AF P&&TTJ G3M1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Cardiac - arrhythmias (including changes in conduction) Cardiac - pulse rate increase, without fall in BP

REFERENCE :

AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 2,144,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

7 mg/kg/1W-I

TOXIC EFFECTS :

Behavioral - muscle contraction or spasticity

REFERENCE :

JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 3,264,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

490 ug/kg

TOXIC EFFECTS :

Behavioral - sleep

REFERENCE :

JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 47,210,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

17 mg/kg

TOXIC EFFECTS :

Behavioral - general anesthetic Behavioral - hallucinations, distorted perceptions Behavioral - convulsions or effect on seizure threshold

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 1,1573,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

75 mg/kg

TOXIC EFFECTS :

Behavioral - coma Cardiac - pulse rate increase, without fall in BP

REFERENCE :

ICMED9 Intensive Care Medicine. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.3- 1977- Volume(issue)/page/year: 11,220,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

12 mg/kg

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :

AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 6,247,1988

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

90 mg/kg

TOXIC EFFECTS :

Behavioral - coma

REFERENCE :

JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 6,199,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

760 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

72 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

170 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

35 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 1,207,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

480 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 1,207,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

125 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 229,163,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

310 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 1,207,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

31 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,782,1973

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

>300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

30 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,601,1973 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

10950 mg/kg/52W-I

TOXIC EFFECTS :

Related to Chronic Data - death

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 112,782,1973

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2800 mg/kg/28D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in bladder weight Endocrine - changes in spleen weight Related to Chronic Data - changes in testicular weight

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 1,207,1975

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

10920 mg/kg/26W-I

TOXIC EFFECTS :

Liver - fatty liver degeneration Endocrine - changes in spleen weight Related to Chronic Data - changes in prostate weight

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 1,207,1975 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

15 mg/kg

SEX/DURATION :

female 13 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - breasts, lactation (prior to or during pregnancy)

REFERENCE :

AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 140,641,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

420 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,567,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

210 mg/kg

SEX/DURATION :

female 9-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 2,69,1976

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

105 mg/kg

SEX/DURATION :

female 7-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 2,69,1976

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

210 mg/kg

SEX/DURATION :

female 7-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 2,69,1976

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

32500 ug/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,555,1978 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4986 No. of Facilities: 58 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 1657 (estimated) No. of Female Employees: 895 (estimated)